Effects of Ile164 polymorphism of beta2-adrenergic receptor gene on coronary artery disease.
OBJECTIVE
This study investigated the relationship between beta(2)-adrenergic receptor (B2AR) Ile164 polymorphism and coronary artery disease (CAD).


BACKGROUND
B2ARs are crucial to the regulation of vascular tone, and neoangiogenesis is impaired in the presence of isoleucine at position 164 (Ile164) B2AR gene polymorphism. No data deal with the role of the variants at position 164 of the B2AR gene in the setting of CAD.


METHODS
The study population consisted of 330 patients undergoing percutaneous coronary intervention (PCI).


RESULTS
The Ile164 polymorphism frequency was higher in CAD (12.1% vs. 3%, p = 0.008) with respect to the control population. We divided our population into 2 groups: group 1 (290 patients, threonine/threonine genotype at position 164 [164Thr/Thr]) and group 2 (40 patients, threonine/isoleucine genotype at position 164 [164Thr/Ile]). Patients of group 2 presented an earlier onset of CAD (56.7 +/- 7.8 vs. 59.5 +/- 10, p = 0.04) and a higher incidence of multivessel disease (25.4% vs. 41%, p = 0.044). At follow-up, group 2 showed a higher incidence of new acute myocardial infarction (17.5% vs. 4.5%, p = 0.001), new PCI (37.5% vs. 13.1%, p < 0.0001), and cardiac death (10% vs. 3.1%, p = 0.036). Cox regression analysis identified Ile164 as an independent predictor of cardiac death (odds ratio [OR]: 3.731, 95% confidence interval [CI]: 1.004 to 13.867, p = 0.049) and an overall major adverse cardiac event (OR: 4.100, 95% CI: 1.945 to 8.640, p = 0.0001). A replication study was done on a population of 150 patients with peripheral artery disease. The presence of the Ile164 allele was associated with a higher incidence of acute myocardial infarction (54.5% vs. 25.2%, p = 0.035) or combined events (acute myocardial infarction, PCI, or coronary artery bypass graft) (63.6% vs. 30.9%, p = 0.027).


CONCLUSIONS
Our study suggests that the B2AR Ile164 mutant is associated with a more aggressive CAD and adversely affects prognosis in patients undergoing PCI.
Piscione
Federico
F
Department of Clinical Medicine, Cardiovascular and Immunology Sciences, Federico II University School of Medicine, Naples, Italy. piscione@unina.it
Iaccarino
Guido
G
Galasso
Gennaro
G
Cipolletta
Ersilia
E
Rao
Maria Assunta
MA
Brevetti
Gregorio
G
Piccolo
Raffaele
R
Trimarco
Bruno
B
Chiariello
Massimo
M
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D003324:Coronary Artery Disease / Q000235:genetics* / Q000628:therapy; D005260:Female; D006801:Humans; D007532:Isoleucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012720:Severity of Illness Index
D018343:Receptors, Adrenergic, beta-2; D007532:Isoleucine